New NIH-funded study on stress-related behaviors has applications to PTSD

Have you ever wondered how you would react in the face of intense trauma? Does your sex have an influence on that? Turns out, the answer is most likely yes.

Assistant Professor of Psychology Rebecca Shansky has been studying behavioral sex differences in response to stress for several years. Through a new project funded by the NIH, Shansky will be working with her friend and colleague from the University of Calgary’s Hotchkiss Brain Institute, Assistant Professor Dr. Matthew Hill. Together, they will attempt to discover the neural mechanisms that underlie sex differences in the way the brain responds to stress.

Hill’s research focuses on the endocannabinoid system, a group of molecules, receptors, and enzymes in the brain that control naturally produced cannabinoids in the brain, or endocannabinoids. Cannabinoids are chemical compound neuromodulators, which work to shape the way neurons respond to basic neurotransmitter signals. Depending on the part of the brain in use, endocannabinoids can have a variety of effects.

With the combined expertise in endocannabinoids and sex differences in stress-related behaviors, the newly funded project will look at ways to increase endocannabinoid signaling to promote stress resilience. Through manipulation of the endocannabinoid system in both female and male rat models, Shansky and Hill hope to see if they can change the sex differences in the behavioral responses to stress.

“I am excited to get into a new system. Endocannabinoids are not something I’ve ever studied or even really thought about before, so in a sense that’s a really exciting, unexplored realm in relation to studying sex differences. We have a lot of translational value in that we could discover a new way to help people with PTSD,” she said, “And of course, I’m thrilled to finally collaborate with one of my best friends.”

The Research

Hall’s lab will be using mass spectrometry, which allows immediate measurements of endocannabinoid signaling levels. Shansky will be completing a combination of behavioral and pharmacological experiments, to see how altering endocannabinoid signals can change the behavioral responses to stressors.

Past research has shown that there are two different forms of stress coping; active and passive. These can often be exhibited through the forced swim test. A rat, model animals known to be excellent swimmers, is put into a bucket of water and if it has an active stress response, it will try to swim to escape, whereas if it has a passive response, it will float until it is rescued. Female rats are more likely to respond actively, while males are more passive. Shansky and Hill believe that these behavioral differences may be mediated by sex differences in endocannabinoid systems. The project focuses on the prefrontal cortex – the center for many complex processes like decision making and emotional regulation. Shansky has determined this to likely be the location where the active or passive response decision is made. By manipulating endocannabinoid signaling in this part of the brain, they hope to see how the rats react in this test and if males are made to be more active, and females act more passive.

The Applications

The results of this research have important applications to humans, in studying people with post-traumatic stress disorder (PTSD). In those who have PTSD, an important aspect to their development is how they responded during the traumatic event. Those who responded passively or had feelings of helplessness are more likely to develop PTSD. Among a cohort of animals, there will be a spectrum of active and passive responses, so potential research could also include looking at the neural coordinates that match with different points on the spectrum to understand those behaviors. Those with active responses may be more likely to be adaptive in the future in the face of new stressors, so if animals can be artificially adapted using the neural coordinates that align with more active responses, perhaps they will be able to respond more actively to the new stress.

Additionally, women are more likely to develop PTSD than men are.

“We’re also using this project to try and understand sex-specific mechanisms that mediate the stress response in males or females. Maybe we can use them to directly to compare to PTSD patients and study in parallel,” Shansky said, “There’s a lot that could come out of this project.”

Their NIH award will help to start off their research for the next year. They hope to receive more future funding for the entire span of this project, with a proposal currently under review. Their research has not yet begun, but Shansky will soon be working with a new postdoctoral researcher and the project will be underway.